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1yon

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Revision as of 04:49, 21 November 2007 by OCA (Talk | contribs)
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1yon, resolution 1.95Å

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Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate

Overview

The crystal structure of Escherichia coli ketopantoate reductase in, complex with 2'-monophosphoadenosine 5'-diphosphoribose, a fragment of, NADP+ that lacks the nicotinamide ring, is reported. The ligand is bound, at the enzyme active site in the opposite orientation to that observed for, NADP+, with the adenine ring occupying the lipophilic nicotinamide pocket., Isothermal titration calorimetry with R31A and N98A mutants of the enzyme, is used to show that the unusual ;reversed binding mode' observed in the, crystal is triggered by changes in the protonation of binding groups at, low pH. This research has important implications for fragment-based, approaches to drug design, namely that the crystallization conditions and, the chemical modification of ligands can have unexpected effects on the, binding modes.

About this Structure

1YON is a Single protein structure of sequence from Escherichia coli with APX as ligand. Active as 2-dehydropantoate 2-reductase, with EC number 1.1.1.169 Full crystallographic information is available from OCA.

Reference

pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study., Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C, Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):171-8. Epub 2007, Jan 16. PMID:17242510

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